Archive | September 2015

Hematopoietic Differentiation Is Required for Initiation of Acute Myeloid Leukemia

Bhaskar Chanda Stem Cell Ye et al. show that myeloid differentiation is required for acquiring a leukemia stem cell (LSC) phenotype and AML initiation and that blocking GMP formation abrogates leukemic transformation. Cytokine-induced bypass of this block restores LSC and AML development, with GMPs providing a genomic environment permissive for activating LSC transcriptional programs.

from Cell Stem Cell http://ift.tt/1LQ592u
via Bhaskar Chanda UHN

Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells

Bhaskar Chanda Stem Cell Induced pluripotency is accompanied by extensive nuclear reprogramming, which is often incomplete during direct interlineage cell conversion. Here, we show overexpression of Gata3, Eomes, and Tfap2c enables a high degree of nuclear reprogramming, independently of pluripotency, and converts mouse fibroblasts into functional induced trophoblast stem-like cells (iTSCs).

from Cell Stem Cell http://ift.tt/1LQ58vk
via Bhaskar Chanda UHN

Direct Induction of Trophoblast Stem Cells from Murine Fibroblasts

Bhaskar Chanda Stem Cell Kubaczka et al. report that transient expression of Tfap2c, Gata3, Eomes, and Ets2 can reprogram murine fibroblasts into induced trophoblast stem cells (iTSCs). iTSCs are fully functional and exhibit full demethylation of key loci, showing that the lineage barrier between somatic and extra-embryonic cell fates can be overcome.

from Cell Stem Cell http://ift.tt/1LQ56nn
via Bhaskar Chanda UHN

CD93 Marks a Non-Quiescent Human Leukemia Stem Cell Population and Is Required for Development of MLL-Rearranged Acute Myeloid Leukemia

Bhaskar Chanda Stem Cell Iwasaki et al. demonstrate that leukemia stem cells (LSCs) in a distinctive genetic subtype of leukemia are non-quiescent. Although human LSCs are typically enriched in the highly quiescent CD34+CD38− phenotypic compartment, co-expression of the lectin CD93 further demarcates LSCs as a discrete subpopulation of actively cycling, non-quiescent AML cells.

from Cell Stem Cell http://ift.tt/1iS9hrA
via Bhaskar Chanda UHN

ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway

Bhaskar Chanda Stem Cell Ho et al. show that ELA is an endogenous peptide hormone produced by human embryonic stem cells that supports self-renewal through auto/paracrine activation of PI3K/AKT signaling. ELA promotes cell-cycle progression and protein translation, prevents apoptosis upon cellular stress, and primes hESCs for endodermal differentiation via activation of TGFβ signaling.

from Cell Stem Cell http://ift.tt/1KjeQbF
via Bhaskar Chanda UHN

HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation

Bhaskar Chanda Stem Cell Qi et al. demonstrate that the inv(16) fusion protein interacts with the tumor suppressor p53 and HDAC8, thereby causing aberrant HDAC8-mediated deacetylation and inactivation of p53. HDAC8 deletion or inhibition selectively depletes LSC activity by reactivating p53, highlighting HDAC8 as an effective therapeutic target to specifically eliminate inv(16) AML LSCs.

from Cell Stem Cell http://ift.tt/1KjeRwm
via Bhaskar Chanda UHN